The principle objective of this research program as set forth in this proposal will be to develop a viable synthetic strategy to the milbemycin-avermectin family of macrolide antibiotics which are known to possess potent activity as broad spectrum antiparasitic agents, in particular anthelmintics. As new synthetic targets we have selected the toxic fungal metabolites known as the talaromycins A and B. Our interest in the talaromycins stem directly from the spiroketal structural unit common to both the avermectins and milbemycins. In addition, we believe we are within reach of a unified synthetic strategy for the lathyrane diterpenes, the simplest member of which is the fungalsidal agent casbene. Representative targets here include bertyadionol and the jolkinols. Each of these projects will require the development of new chemistry and synthetic methodology, which will have utility not only to the above specific targets but to the synthesis of important new pahrmacological agents in general.